1. Field of the Invention
This invention relates to instruments and methods for performing non-invasive measurements of analyte concentrations and for monitoring, analyzing and regulating tissue status, such as tissue glucose levels.
2. Description of the Background
Diabetes is a chronic life threatening disease for which there is presently no cure. It is the fourth leading cause of death by disease in the United States and at least 175 million people worldwide are estimated to be diabetic. Diabetes is a disease in which the body does not properly produce or respond to insulin. The high glucose concentrations that can result from this affliction can cause severe damage to vital organs, such as the heart, eyes and kidneys.
Type I diabetes (juvenile diabetes or insulin-dependent diabetes mellitus) is the most severe form of the disease, comprising approximately 10% of the diabetes cases in the United States. Type I diabetics must receive daily injections of insulin in order to sustain life. Type B diabetes, (adult onset diabetes or non-insulin dependent diabetes mellitus) comprises the other 90% of the diabetes cases. Type II diabetes is often manageable with dietary modifications and physical exercise, but may still require treatment with insulin or other medications. Because the management of glucose to near-normal levels can prevent the onset and the progression of complications of diabetes. Persons afflicted with either form of the disease are instructed to monitor their blood glucose concentration in order to assure that the appropriate level is achieved and maintained.
Traditional methods of monitoring the blood glucose concentration of an individual require that a blood sample be taken. This method can be painful, inconvenient, costly, and pose the risk of infection. Another glucose measuring method involves urine analysis, which, aside from being inconvenient, may not reflect the current status of the patient's blood glucose because glucose appears in the urine only after a significant period of elevated levels of blood glucose. An additional inconvenience of these traditional methods is that they require testing supplies such as collection receptacles, syringes, glucose measuring devices and test kits. Although disposable supplies have been developed, they are costly and can require special methods for disposal.
Many attempts have been made to develop a painless, non-invasive external device to monitor glucose concentrations. Various approaches have included electrochemical and spectroscopic technologies, such as near-infrared spectroscopy and Raman Spectroscopy. Despite extensive efforts, however, none of these methods has, so far, yielded a non-invasive device or method for the in vivo measurement of glucose that is sufficiently accurate, reliable, convenient and cost-effective for routine use.
The phenomenon of endogenous skin fluorescence, as well as endogenous fluorescence of other biological tissues, has been well documented in the literature. Methods for non-invasively measuring skin fluorescence have been developed and incorporated into commercially available instruments (e.g. Skin Skan or Fluorolog). In skin, important fluorophores include tryptophan-containing proteins, which fluoresces in the 350-450 nm region, and fluorophores associated with collagen cross links, skin oils, NADH, FAD, other flavoproteins, elastin, and quinones, which fluoresce in a broad region from 420 to 650 nm (J. Invest. Dermatol. 111:776-780, 1998, and references therein).
Fluorescence has been used to predict malignancies in tissue, e.g., cervical tissue, bladder tissue, and the buccal cavity. Fluorescence of dyes (fluorescence associated with dyes that selectively bind to biological compounds) has also been used to study in vivo cellular processes.